From structure to sequence: Antibody discovery using cryoEM

被引：28

作者：

Antanasijevic, Aleksandar ^{[1
,2
]}

Bowman, Charles A. ^{[1
,2
]}

Kirchdoerfer, Robert N. ^{[3
]}

Cottrell, Christopher A. ^{[2
,4
]}

Ozorowski, Gabriel ^{[1
,2
]}

Upadhyay, Amit A. ^{[5
,6
,7
]}

Cirelli, Kimberly M. ^{[8
]}

Carnathan, Diane G. ^{[6
,7
]}

Enemuo, Chiamaka A. ^{[6
,7
]}

Sewall, Leigh M. ^{[1
]}

Nogal, Bartek ^{[1
]}

Zhao, Fangzhu ^{[4
,9
]}

Groschel, Bettina ^{[2
,4
]}

Schief, William R. ^{[2
,4
,10
,11
]}

Sok, Devin ^{[2
,4
,9
]}

Silvestri, Guido ^{[6
,7
]}

Crotty, Shane ^{[8
]}

Bosinger, Steven E. ^{[5
,6
,7
]}

Ward, Andrew B. ^{[1
,2
]}

机构：

[1] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Consortium HIV AIDS Vaccine Dev CHAVD, La Jolla, CA 92037 USA

[3] Univ Wisconsin, Coll Agr & Life Sci, Dept Biochem, Madison, WI 53706 USA

[4] Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA

[5] Emory Univ, Emory Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30329 USA

[6] Emory Univ, Yerkes Natl Primate Res Ctr, Yerkes Div Microbiol & Immunol, Atlanta, GA 30329 USA

[7] Emory Univ, Yerkes Nonhuman Primate Genom Core, Atlanta, GA 30329 USA

[8] La Jolla Inst Immunol, Vaccine Discovery Div, La Jolla, CA 92037 USA

[9] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA

[10] MIT, Ragon Inst, Massachusetts Gen Hosp, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[11] Harvard Univ, Cambridge, MA 02139 USA

来源：

SCIENCE ADVANCES | 2022年 / 8卷 / 03期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

MONOCLONAL-ANTIBODIES; NONHUMAN-PRIMATES; HIV; RESPONSES; IDENTIFICATION; IMMUNOGLOBULIN; VISUALIZATION; TECHNOLOGIES; GENERATION;

D O I：

10.1126/sciadv.abk2039

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

One of the rate-limiting steps in analyzing immune responses to vaccines or infections is the isolation and characterization of monoclonal antibodies. Here, we present a hybrid structural and bioinformatic approach to directly assign the heavy and light chains, identify complementarity-determining regions, and discover sequences from cryoEM density maps of serum-derived polyclonal antibodies bound to an antigen. When combined with next-generation sequencing of immune repertoires, we were able to specifically identify clonal family members, synthesize the monoclonal antibodies, and confirm that they interact with the antigen in a manner equivalent to the corresponding polyclonal antibodies. This structure-based approach for identification of monoclonal antibodies from polyclonal sera opens new avenues for analysis of immune responses and iterative vaccine design.

引用

页数：11

共 50 条

[1] Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM
Antanasijevic, Aleksandar
Sewall, Leigh M.
Cottrell, Christopher A.
Carnathan, Diane G.
Jimenez, Luis E.
Ngo, Julia T.
Silverman, Jennifer B.
Groschel, Bettina
Georgeson, Erik
Bhiman, Jinal
Bastidas, Raiza
LaBranche, Celia
Allen, Joel D.
Copps, Jeffrey
Perrett, Hailee R.
Rantalainen, Kimmo
Cannac, Fabien
Yang, Yuhe R.
de la Pena, Alba Torrents
Rocha, Rebeca Froes
Berndsen, Zachary T.
Baker, David
King, Neil P.
Sanders, Rogier W.
Moore, John P.
Crotty, Shane
Crispin, Max
Montefiori, David C.
Burton, Dennis R.
Schief, William R.
Silvestri, Guido
Ward, Andrew B.
[J]. NATURE COMMUNICATIONS, 2021, 12 (01)
[2] Structural and functional evaluation ofde novo-designed, two-component nanoparticle carriers for HIV Env trimer immunogens
Antanasijevic, Aleksandar
Ueda, George
Brouwer, Philip J. M.
Copps, Jeffrey
Huang, Deli
Allen, Joel D.
Cottrell, Christopher A.
Yasmeen, Anila
Sewall, Leigh M.
Bontjer, Ilja
Ketas, Thomas J.
Turner, Hannah L.
Berndsen, Zachary T.
Montefiori, David C.
Klasse, Per Johan
Crispin, Max
Nemazee, David
Moore, John P.
Sanders, Rogier W.
King, Neil P.
Baker, David
Ward, Andrew B.
[J]. PLOS PATHOGENS, 2020, 16 (08)
[3] Barad BA, 2015, NAT METHODS, V12, P943, DOI [10.1038/nmeth.3541, 10.1038/NMETH.3541]
[4] Visualization of the HIV-1 Env glycan shield across scales
Berndsen, Zachary T.
Chakraborty, Srirupa
Wang, Xiaoning
Cottrell, Christopher A.
Torres, Jonathan L.
Diedrich, Jolene K.
Lopez, Cesar A.
Yates, John R., III
van Gils, Marit J.
Paulson, James C.
Gnanakaran, Sandrasegaram
Ward, Andrew B.
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (45) : 28014 - 28025
[5] Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles
Brouwer, Philip J. M.
Antanasijevic, Aleksandar
de Gast, Marlon
Allen, Joel D.
Bijl, Tom P. L.
Yasmeen, Anila
Ravichandran, Rashmi
Burger, Judith A.
Ozorowski, Gabriel
Torres, Jonathan L.
LaBranche, Celia
Montefiori, David C.
Ringe, Rajesh P.
van Gils, Marit J.
Moore, John P.
Klasse, Per Johan
Crispin, Max
King, Neil P.
Ward, Andrew B.
Sanders, Rogier W.
[J]. NPJ VACCINES, 2021, 6 (01)
[6] Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability
Brouwer, Philip J. M.
Caniels, Tom G.
van der Straten, Karlijn
Snitselaar, Jonne L.
Aldon, Yoann
Bangaru, Sandhya
Torres, Jonathan L.
Okba, Nisreen M. A.
Claireaux, Mathieu
Kerster, Gius
Bentlage, Arthur E. H.
van Haaren, Marlies M.
Guerra, Denise
Burger, Judith A.
Schermer, Edith E.
Verheul, Kirsten D.
van der Velde, Niels
van der Kooi, Alex
van Schooten, Jelle
van Breemen, Marielle J.
Bijl, Tom P. L.
Sliepen, Kwinten
Aartse, Aafke
Derking, Ronald
Bontjer, Ilja
Kootstra, Neeltje A.
Wiersinga, W. Joost
Vidarsson, Gestur
Haagmans, Bart L.
Ward, Andrew B.
de Bree, Godelieve J.
Sanders, Rogier W.
van Gils, Marit J.
[J]. SCIENCE, 2020, 369 (6504) : 643 - +
[7] Antibody Structure and Function: The Basis for Engineering Therapeutics
Chiu, Mark L.
Goulet, Dennis R.
Teplyakov, Alexey
Gilliland, Gary L.
[J]. ANTIBODIES, 2019, 8 (04)
[8] Slow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance
Cirelli, Kimberly M.
Carnathan, Diane G.
Nogal, Bartek
Martin, Jacob T.
Rodriguez, Oscar L.
Upadhyay, Amit A.
Enemuo, Chiamaka A.
Gebru, Etse H.
Choe, Yury
Viviano, Federico
Nakao, Catherine
Pauthner, Matthias G.
Reiss, Samantha
Cottrell, Christopher A.
Smith, Melissa L.
Bastidas, Raiza
Gibson, William
Wolabaugh, Amber N.
Melo, Mariane B.
Cossette, Benjamin
Kumar, Venkatesh
Patel, Nirav B.
Tokatlian, Talar
Menis, Sergey
Kulp, Daniel W.
Burton, Dennis R.
Murrell, Ben
Schief, William R.
Bosinger, Steven E.
Ward, Andrew B.
Watson, Corey T.
Silvestri, Guido
Irvine, Darrell J.
Crotty, Shane
[J]. CELL, 2019, 177 (05) : 1153 - +
[9] Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates
Cottrell, Christopher A.
van Schooten, Jelle
Bowman, Charles A.
Yuan, Meng
Oyen, David
Shin, Mia
Morpurgo, Robert
van der Woude, Patricia
van Breemen, Marielle
Torres, Jonathan L.
Patel, Raj
Gross, Justin
Sewall, Leigh M.
Copps, Jeffrey
Ozorowski, Gabriel
Nogal, Bartek
Sok, Devin
Rakasz, Eva G.
Labranche, Celia
Vigdorovich, Vladimir
Christley, Scott
Carnathan, Diane G.
Sather, D. Noah
Montefiori, David
Silvestri, Guido
Burton, Dennis R.
Moore, John P.
Wilson, Ian A.
Sanders, Rogier W.
Ward, Andrew B.
van Gils, Marit J.
[J]. PLOS PATHOGENS, 2020, 16 (08)
[10] Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization
de la Pena, Alba Torrents
Julien, Jean-Philippe
de Taeye, Steven W.
Garces, Fernando
Guttman, Miklos
Ozorowski, Gabriel
Pritchard, Laura K.
Behrens, Anna-Janina
Go, Eden P.
Burger, Judith A.
Schermer, Edith E.
Sliepen, Kwinten
Ketas, Thomas J.
Pugach, Pavel
Yasmeen, Anila
Cottrell, Christopher A.
Torres, Jonathan L.
Vavourakis, Charlotte D.
van Gils, Marit J.
LaBranche, Celia
Montefiori, David C.
Desaire, Heather
Crispin, Max
Klasse, Per Johan
Lee, Kelly K.
Moore, John P.
Ward, Andrew B.
Wilson, Ian A.
Sanders, Rogier W.
[J]. CELL REPORTS, 2017, 20 (08): : 1805 - 1817

← 1 2 3 4 5 →